Thermal injury-induced immunosuppression in mice: the role of macrophage-derived reactive nitrogen intermediates.
Macrophages (Mphi) have been implicated in the suppression of lymphocyte function following thermal injury. Splenocytes isolated from C57BL/ 6NCR female mice 4-7 days after thermal injury displayed suppressed proliferative responses to Concanavalin A (ConA) and lipopolysaccharide (LPS) and high levels of reactive nitrogen intermediate (RNI) production. Inhibition of nitric oxide synthase activity with NG-monomethyl-L-arginine restored ConA responses but not LPS responses. Surprisingly, ConA-stimulated interferon-gamma (IFN-gamma) production was increased in splenocytes from injured mice. IFN-gamma contributed to the RNI-mediated immunosuppression as antibodies against IFN-gamma reduced RNI production and immunosuppression. ConA-stimulated co-cultures of splenic Mphi from injured mice and normal splenocytes produced high levels of RNI only under conditions of cellular contact and splenic Mphi from injured mice were capable of suppressing normal splenocytes responses in co-culture. These results indicate that Mphi activity and specifically RNI production contribute to the suppression of T lymphocyte function after thermal injury.
Schwacha
M G
MG
Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence 02903, USA.
Somers
S D
SD
D000818:Animals; D002056:Burns / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009589:Nitrogen Oxides / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016207:Cytokines; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009589:Nitrogen Oxides; D003208:Concanavalin A; D019323:omega-N-Methylarginine; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase